Find JAK-STAT signaling pathway primary antibodies, antibody pairs, ELISAs and Luminex® assays by protein
Key JAK-STAT Pathway Targets
Four JAK family kinases, including JAK1, JAK2, JAK3, and TYK2, and seven STAT family members, including STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6, have been identified. JAK1, JAK2, and TYK2 appear to be ubiquitously expressed, while JAK3 expression is normally limited to lymphoid cells. The JAKs are structurally unique in having a C-terminal kinase domain (JH1) preceded by a pseudokinase domain (JH2), which lacks the catalytic activity but has a critical regulatory function. JAKs also have a Src homology 2 (SH2) domain and an N-terminal band four-point-one, ezrin, radixin, moesin (FERM) domain that is critical for mediating the association with cytokine receptors. STAT proteins contain a SH2 domain for dimerization and a DNA-binding domain. The amino acid sequence diversity and their tissue-specific distributions account for the diverse roles of STATs in response to extracellular cytokines.1-2 The JAK-STAT pathways are up-regulated by a vast array of cytokines/growth factors. One mechanism for negative regulation of JAK-STAT pathways is through suppresser of cytokine signaling (SOCS) proteins, which directly bind to and inactivate JAKs3, and protein inhibitors of activated STATs (PIAS) that bind to phosphorylated STAT dimers, preventing DNA binding.4
Abnormal constitutive activation of JAK-STAT pathways has been implicated in various cancers and immune disorders. For example, STAT3 is persistently activated in many tumors, including major carcinomas and some hematologic tumors.5 Activating mutations in JAK2 have been linked to leukemia. TEL-JAK2 fusion due to chromosomal translocation was identified in a small set of human T cell acute lymphoblast leukemia patients.6 The V617F mutation in the JH2 pseudo-kinase domain of JAK2 was found in a high percentage of patients with myeloproliferative disorders, including polycythaemia vera.7 Inhibitors of JAK-STAT pathways are currently being sought in the areas of oncology and immune disorders.
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Flow cytometry of Jurkat cells labeled with rabbit anti-STAT4. Jurkat cells were fixed and permeabilized using FIX & PERM® reagents.
Cells were stained with (black trace) or without (blue trace) 0.5 μg anti-STAT4 followed by Alexa Fluor® 488 goat anti-rabbit Ig. Pre-incubation with immunogenic peptide decreased the signal (red trace). Data were generated using a Novex® STAT4 ABfinity™ Recombinant Rabbit Monoclonal Antibody (700185).
Expression of STAT5b (pY699) in TF-1 cells. TF-1 cells were treated with IFN-α or IL-3, or left unstimulated.
Total ELISA kits make effective controls. Cell extracts were prepared and analyzed with the STAT5a [pY694] ELISA and STAT5a (Total) ELISA kits.
Phosphorylation of STAT5a is increased in sodium vanadate-treated HEL cells, whereas the total level of STAT5a remains relatively constant in treated vs. untreated control, demonstrating the utility of the Total ELISA kits as controls. Data were generated using a Novex®
STAT5a [pY694] ELISA Kit (KHO0761) and
STAT5a (Total) ELISA Kit (KHO0751).
Events leading to STAT activation.
|KPNA1 (NPI-1)||RELA (NFκB)||SUMO1|
|ALK||F2R (Par1)||KDR (CD309)|
|AXL (UFO)||F2RL2||KIT (CD117)|
|CD4||FGFR3 (CD333)||MST1R (CD136)|
|CSF1R (CD115)||FLT1||NGFR (CD27)1|
|CXCR4 (CD184)||FLT3 (CD135)||NTRK1|
|EPHA1||IFNAR2 (CD118)||PDGFRA (CD140a)|
|EPHA2||IFNGR1 (CD119)||PDGFRB (CD140b)|
|EPHA7||IL2RG (CD132)||TNFRSF10A (CD120a)|
|EPHA8||IL3RA (CD123)||TNFRSF10B (CD262)|
|EPHB1||IL4R (CD124)||TNFRSF1A (CD120a)|
|EPHB2||IL6R (CD126)||TNFRSF1B (CD120b)|
|ERBB2 (Her2)||INSR (CD220)|
|CCL21 (6Ckine)||IL1A||TNFSF10 (TRAIL)|
|CCL25 (TECK)||IL1B||TNFSF13B (BAFF)|
- Aaronson, D.S. et al. (2002) Science 296: 1653-1655.
- O’Shea, J.J. et al. (2004) Nat Rev Drug Discovery 3: 555-564.
- Kishimoto, T. et al. (2001) Nat Genetics 28: 4-5.
- Shuai, K. et al. (2000) Oncogene 19 : 2638-2645.
- Darnell, J.E. et al. (2005) Nat Medicine 11: 595-596.
- Lacronique, V. et al. (1997) Science 278: 1309-1312.
- Ferrajoli, A. et al. (2006) Curr Cancer Drug Targets 6: 671-679.
* This promotion is open to customers in the US and Canada. Discount will apply to orders received by Life Technologies no later than September 30, 2013, or until promotional supplies are depleted, whichever comes first. Customer can use the discount only once. Discount only applies to a maximum of 1 kit per customer. Discount applies to list price in effect at the time order is received by Life Technologies. Cannot be combined with other discounts or promotions. Offer void where prohibited, licensed, or restricted by federal, state, provincial, or local laws or regulation or agency/institutional policy. Other restrictions may apply.
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